Myocardial Protection in Patients With Post-acute Inflammatory Cardiac Involvement Due to COVID-19

• Status: Enrolling by invitation
• Trial end date: 2028-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Postacute sequelae of COVID-19 infection (PASC) are increasingly recognised complications and are defined by lingering symptoms, not present prior to the infection, typically persisting for more than 4 weeks. Cardiac symptoms due to post-acute inflammatory cardiac involvement affect a broad segment of people, who were previously well and may have had only mild acute illness (PASC-cardiovascular syndrome, PASC-CVS). Symptoms may be contiguous with the acute illness, however, more commonly they occur after a delay. Symptoms related to the cardiovascular system include exertional dyspnoea, exercise intolerance chest tightness, pulling or burning chest pain, and palpitations. Phenotypically, it is characterised by chronic perivascular and myopericardial inflammation. Cardiac symptoms may be accompanied by manifestations of other organ systems, including fatigue, brain fog, myalgias, skin and joint manifestations, etc, now commonly referred to as the Long COVID or PASC syndrome.

Early intervention with immunosuppression and antiremodelling therapy may reduce symptoms and myocardial impairment, by minimising the disease activity and inducing disease remission. Low dose maintenance therapy may help to maintain the disease activity at the lowest possible level. Clinical trials of immunosuppression in patients with viral myocarditis in advanced stages of heart failure have not shown an improved outcome, however there was an improvement of LVEF with antiremodelling therapy in patients with reduced function. The benefits of early initiations of antiremodelling therapy to reduce symptoms of exercise intolerance are well recognised, but not commonly employed outside the contexts of heart failure or hypertension. As most patients with inflammatory heart disease only have mild and nonspecific symptoms and few or no structural abnormalities, they are left untreated (standard of care). The aim of this study is to examine the efficacy of a combined immunosuppressive/antiremodelling therapy in patients with PASC symptoms and inflammatory cardiac involvement determined by CMR, to reduce the symptoms and inflammatory myocardial injury and thereby stop the progression to reduced LVEF, HF and death.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Valentina Puentmann
• Collaborators: Alcedis GmbH; Bayer
• Treatments: Losartan; Prednisolone

Criteria

Inclusion Criteria:

• Patients ≥ 18 years

• Patients with documented recent COVID19 infection (>4 weeks and <6 months)

• PASC Syndrome, defined by persistence or new symptoms, not present prior to the infection.

• CMR evidence of inflammatory cardiac involvement at BL by any of the following criteria:

• Increased native T1≥ 1130 ms at 3.0 Tesla (or 1030 ms at 1.5 Tesla) and/or;

• Increased native T2 ≥39.5 ms at 3.0 Tesla (or 49.5 at 1.5 Tesla) and/or

• present non-ischaemic myopericardial LGE and/or;

• LVEF ≥45 - ≤50%.

• Willingness to comply with the study procedures and study protocol

Exclusion Criteria:

• Severe acute COVID illness requiring hospitalisation

• Known allergy to or intolerance of the study medications

• Symptomatic hypotension (systolic blood pressure less than 90 mm Hg), not reversible with oral hydration

• Any previous or current use of ACE inhibitors, AR Blockers

• Any previous oral prednisolone, or any other immunosuppressive or biological treatment (within 6 months)

• History or CMR evidence of pre-existing significant heart disease, including:

1. Known cardiac impairment with LVEF ≤44%

2. Congestive heart failure (NYHA III-IV)

3. Active heart failure treatment

4. Established ischaemic heart disease, peripheral arterial disease and/or cerebrovascular disease

5. Persistent or permanent atrial fibrillation or significant heart rhythm abnormalities

6. Congenital or clinically relevant valvular heart disease (moderate or severe)

7. Specific cardiomyopathy (hypertrophic, hypertensive heart disease, amyloidosis, previous myocarditis, non-ischaemic dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, non-compaction cardiomyopathy, etc).

• Known significant concomitant diseases that are likely to interfere with the evaluation of the patient's safety and of the study outcome (e.g. diabetes, lung or hepatic disease, epilepsy, psychiatric disorders, renal disease with a current estimated GFR <30 mL/min/1.73 m² using MDRD formula, chronic systemic infection or immunocompromise)

• Exceeding scanner bore and table-holding capacity: Weight >125 kg, BMI > 35 kg/m2

• Contraindications to contrast-enhanced CMR imaging, e.g.

1. MR-unsafe implantable device

2. known allergy to gadolinium-based contrast agent (CBGA)

• For female participants:

1. Pregnant or breastfeeding women

2. Persons of childbearing potential not willing to use effective contraception (defined as PEARL index <1 - e.g. contraceptive pill, IUD)

• Known alcohol, drug or chemical abuse

• Patients currently participating in an investigational study or for whom participation is planned.

• Unable to provide written informed consent

Patients with CMR evidence of structural heart disease or incidental heart rhythm abnormalities will be advised to see their own doctor for further investigation.